Expression of Cathepsin B, D and L Protein in Juvenile Idiopathic Arthritis

Abstract

Juvenile idiopathic arthritis (JIA) is the most common childhood autoimmune rheumatic disease and like rheumatoid arthritis (RA), it is characterized by inflammation and the progressive destruction of joints. In RA, cathepsins as proteinases play a major role in destroying synovial tissue and cartilage matrix. So far no data on cathepsin expression in pannus tissue of HA patients exist. The aim of this study was to characterize the expression levels of cathepsins B, D, H, and L in HA and to compare them with those in RA. Synovectomy tissue from 16 HA and 12 RA patients was investigated for cathepsin expression levels by Western blot analysis. Expression of cathepsins B, D and L was on comparable levels in the synovectomy tissue of HA and RA patients. The following graduation of expression was determined: cathepsin D > cathepsin L > cathepsin B. Cathepsin H was neither found to be expressed in HA nor in RA patients. The expression levels of cathepsins in pannus tissue showed no clear difference between patients with systemic JIA and patients with monoarticular JIA. In summary, the comparable expression of cathepsins B, D and L in RA and JIA synovectomy tissue suggests that they may play a similarly important role in destroying synovial tissue and cartilage matrix in the course of HA and RA.

Analyses of differential proteome of human synovial fibroblasts obtained from arthritis

“…The cysteine proteases cathepsin B and cathepsin L, particularly, have been shown to be activated by proto-oncogenes and upregulated in RA synovium at sites of cartilage invasion [20]. The aspartate protease cathepsin D has not been studied in much detail with respect to arthritis in contrast to cathepsins B and L. However, cathepsin D has been purified from RA synovium and has been demonstrated in RA and OA synovial fluid [21]. Cathepsin D has also been found to be overexpressed in OA's SFs as compared with that in RA's SFs in our experiment.…”

Cysteine Proteases

“…Cathepsins of the papain family seem to play a critical role in rheumatoid arthritis (Taubert et al, 2002) and atherosclerosis (Lecaille et al, 2002;Otto and Schirmeister, 1997).…”

cAMP-response element binding protein (CREB) regulates cyclosporine-A-mediated down-regulation of cathepsin B and L synthesis

“…Cathepsin B and L are cysteine proteases that have been implicated in a number of inflammatory diseases, such as rheumatoid arthritis (Taubert et al 2002) and cancer progression (Janulis et al 1999). The main function of the cathepsins is the degradation of proteins that have entered the lysosomal system from outside via endocytosis or phagocytosis (Everts et al 1996).…”